1. Field of the Invention
This invention pertains to analogues of cholecystokinin-8 (CCK-8) having high receptor selectivity. Specific amino acid sequence replacements preserve the activity of CCK-8, but allow for receptor selectivity.
2. Background of the Invention
CCK-8, having an amino acid sequence of Asp-Tyr-(SO.sub.3.sup.-)-Met-Gly-Trp-Met-Asp-Phe-NH.sub.2, has been identified as having a wide variety of biological activities. Thus, regulation of pancreatic secretion, gall bladder contraction and gut motility all appear to be at least influenced by CCK-8 release.
Additionally, this hormone is found in high concentrations in the brains of mammals, including humans, and is implicated in a wide variety of neuro-transmitter activities. The list of therapeutic uses for this hormone include control of satiety and gut functions, as well as treatment of a variety of neurological disorders, e.g., treatment of psychotic disfunction. It appears that a plurality of chemo receptors for this compound are found in the brain and the gut.
To realize the therapeutic potential offered by CCK-8, it is necessary to obtain a pharmacologically acceptable compound at least preserving the activity of the natural compound at a particular receptor, but eliminating or drastically reducing activity at other different possible receptors reactive therewith, to control side effects.